We have continued our work on theoretical, experimental, and computational aspects of light -tissue interactions for non-invasive quantitative optical imaging and spectroscopy. Researchers at PTB of Berlin provided us time of flight measurements in transillumination geometry of breast images in two wavelengths (670 and 780nm). We have applied our methodology known as time-dependent contrast functions, to quantify the size and the optical properties of the normal tissue background and those of the tumor localized by standard mammography. We were successfully able to find the exact location, estimate the size, and retrieve the scattering and the absorption coefficients of the tumor and those of the background. Using the absorption spectra of oxy- and deoxy-hemoglobin, we were able to estimate the oxygen saturation and the total blood volume of the tumor and background tissue from the absorption coefficients at 670 and 780nm. Work is underway to study the effects of boundaries on the images. In order to avoid incisional biopsy in the oral cavity, a theoretical framework has been developed to quantify the thickening of the epithelial layer in oral mucosa non-invasively. We have developed a spectroscopic device which uses an oblique angle reflectance setting and started to be used in a Phase II clinical trial (designed by NCI) for the non-invasive study of inflammation and effects of chemopreventative drugs. The results from a patient with leukoplakia compared to that obtained from a normal subject show qualitatively the prediction of the theory. Work is underway to screen more patients and make the measurement more quantitative.We are pursuing the use of exogenous and endogenous fluorescent markers to be able to achieve specificity of the spectroscopic signatures of the tissue abnormality under investigation. In collaboration with the University of Tel-Aviv, we have been awarded a BSF grant to continue our research on practical implementation of our previously developed 3D reconstruction algorithm which localizes the position and the concentration of fluorophore masses. Our inverse algorithm will be used to find the position and the concentration of liposomes filled with fluorescent particles as a model for localized fluorescent masses in vivo.. Along these line of research, we are testing an analytical theory of photon migration to retrieve the life-time of biological analytes by using phantom experiments. We are continuing a collaboration with researchers at NCI to study the practical use of our photon migration theory in the development of a guided biopsy infrared fluorescence imaging system for sentinel node detection in breast cancer using fluorescent particles.